1. Field of the Invention
The present invention relates to a system for determining the volume of a liquid. More particularly, the present invention relates to volume dispensing systems which dispense varied liquids.
2. Description of the Prior Art
Multichannel volume dispensing devices, such as automated liquid handling (ALH) systems, are widely used in drug discovery assays and other high-throughput screening processes. Multichannel volume dispensing devices are also referred to herein as liquid handlers and as dispensing systems. The performance of these systems is heavily based on the ability to accurately and precisely deliver volumes of specific reagents. For instance, because concentrations of species within an assay are volume-dependent, assay integrity and the subsequent interpretation of assay results are directly tied to the accuracy of the delivered volume, which is ultimately tied to ALH performance. This direct connection between assay results and ALH performance demonstrates an imperative need to ensure proper performance of ALH equipment, especially for critically important assays.
There is, however, much to consider when choosing the best method for calibrating dispensing devices. For one, volumes that must be accurately and precisely delivered are typically small, so the method of calibration selected must be particularly effective for measuring small volumes. Further, it is important that results produced by the method be standardized, or more specifically, traceable to national standards to achieve consistent volumetric delivery performance among all dispensing devices regardless of make, model, manufacturer or location of the device. It is also important that the method be robust, rapid, and easy to use in the laboratory by in-house personnel so that the volumetric performance of the device can be verified frequently and with minimal device downtime. This need to be efficient is especially critical for multichannel device calibration, since for these devices, calibration must be performed not once, but for each channel separately to assure accuracy and precision within the entire device. For purposes of the present invention description, calibration of a device includes verification and/or validation of the device.
Prior methods of determining liquid volume, including those designed to satisfy the aforementioned considerations, are well-documented. Several of these methods, such as gravimetric, fluorometric and photometric approaches, have been used to calibrate liquid handling systems with varying degrees of success. A thorough description of these methods is presented in U.S. Pat. No. 6,741,365 issued to Curtis (“the Curtis '365 Patent”), which is incorporated entirely herein. Although widely used, gravimetric analysis generally does not provide information about individual channel performance for multichannel dispensing devices and is difficult to perform at low volumes. By comparison, a fluorescence approach gives information about each channel and readily extends to low volumes. However, the well-known variability inherent in fluorescent dyes caused by quenching and photobleaching makes an accurate volume determination difficult to achieve. These limitations also make standardization of fluorescence approaches difficult to achieve, and have hindered the development of internationally recognized fluorescence standards. As with fluorescence, a photometric approach provides information about each channel, but more importantly the photometric approach allows for volume measurements which are traceable to national and international standards.
Added to the limitations of these prior methods is the problem that none is particularly well-suited for calibrating liquid handling devices to precisely and accurately dispense any, or all, liquid types. Indeed, the ability of a liquid handler to properly dispense can vary from liquid-to-liquid. While liquid handling instruments are capable of dispensing a wide array of reagent types, it is commonly known that performance parameters can vary significantly between different solvent types (e.g., aqueous, organic, serum, etc.). A dispensing device which precisely and accurately delivers an aqueous-based liquid, water, for example, may not be as precise and as accurate in dispensing an organic-based liquid, dimethyl sulfoxide (DMSO), for example. Thus, a methodology used for aqueous-based samples may dispense a significantly different amount of volume if employed for an organic-based solution of different characteristics. Liquid handler software packages incorporating computational algorithms may provide users with the ability to adjust dispense methodologies to compensate for solvent-dependent performance differences. However, unless an accurate measurement of the liquid handler performance is collected, these parameters could lead to a false-sense of performance when a reagent from a different solvent-type is employed. In particular, prior methods for calibrating delivery devices are not optimally designed for calibrating liquid handlers to dispense liquids which are non-aqueous and/or complex. As discussed herein, the term complex is used to refer to any liquid type (aqueous, organic, etc.) that has one or more components and/or additives, such as dyes, other liquid types, salts, sugars, detergents, surfactants, proteins, bio- or cellular-based materials, chelating agents, inorganic materials, etc.
Therefore, what is needed is a system and related method to precisely and accurately determine the volume of aqueous, complex, non-aqueous, or complex and non-aqueous liquids that are dispensed from a liquid handling device. The system should include one or more of a determination method, an apparatus, and a kit combining an apparatus and instructions for carrying out the method. The system and related method should be suitable for combining a liquid or solution of interest for use in a liquid handler with a liquid or solution including one or more dyes suitable for photometric or other volume measurement techniques.